CYBR1_RAT
ID CYBR1_RAT Reviewed; 286 AA.
AC Q5RKJ2;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Plasma membrane ascorbate-dependent reductase CYBRD1 {ECO:0000250|UniProtKB:Q53TN4};
DE EC=7.2.1.3 {ECO:0000250|UniProtKB:Q53TN4};
DE AltName: Full=Cytochrome b reductase 1;
DE AltName: Full=Duodenal cytochrome b {ECO:0000303|PubMed:16510471};
GN Name=Cybrd1 {ECO:0000312|RGD:1305740};
GN Synonyms=Dcytb {ECO:0000303|PubMed:16510471};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=16510471; DOI=10.1152/ajplung.00342.2005;
RA Turi J.L., Wang X., McKie A.T., Nozik-Grayck E., Mamo L.B., Crissman K.,
RA Piantadosi C.A., Ghio A.J.;
RT "Duodenal cytochrome b: a novel ferrireductase in airway epithelial
RT cells.";
RL Am. J. Physiol. 291:L272-L280(2006).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=17627967; DOI=10.1152/ajpgi.00579.2006;
RA Frazer D.M., Wilkins S.J., Anderson G.J.;
RT "Elevated iron absorption in the neonatal rat reflects high expression of
RT iron transport genes in the distal alimentary tract.";
RL Am. J. Physiol. 293:G525-G531(2007).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Plasma membrane reductase that uses cytoplasmic ascorbate as
CC an electron donor to reduce extracellular Fe(3+) into Fe(2+). Probably
CC functions in dietary iron absorption at the brush border of duodenal
CC enterocytes by producing Fe(2+), the divalent form of iron that can be
CC transported into enterocytes. It is also able to reduce extracellular
CC monodehydro-L-ascorbate and may be involved in extracellular ascorbate
CC regeneration by erythrocytes in blood. May also act as a ferrireductase
CC in airway epithelial cells (By similarity). May also function as a
CC cupric transmembrane reductase (By similarity).
CC {ECO:0000250|UniProtKB:Q53TN4, ECO:0000250|UniProtKB:Q925G2}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Fe(3+)(out) + L-ascorbate(in) = Fe(2+)(out) + H(+) +
CC monodehydro-L-ascorbate radical(in); Xref=Rhea:RHEA:30403,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:38290, ChEBI:CHEBI:59513; EC=7.2.1.3;
CC Evidence={ECO:0000250|UniProtKB:Q53TN4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30404;
CC Evidence={ECO:0000250|UniProtKB:Q53TN4};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cu(2+)(out) + L-ascorbate(in) = Cu(+)(out) + H(+) +
CC monodehydro-L-ascorbate radical(in); Xref=Rhea:RHEA:66656,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29036, ChEBI:CHEBI:38290,
CC ChEBI:CHEBI:49552, ChEBI:CHEBI:59513;
CC Evidence={ECO:0000250|UniProtKB:Q925G2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66657;
CC Evidence={ECO:0000250|UniProtKB:Q925G2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-ascorbate(in) + monodehydro-L-ascorbate radical(out) = L-
CC ascorbate(out) + monodehydro-L-ascorbate radical(in);
CC Xref=Rhea:RHEA:66524, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513;
CC Evidence={ECO:0000250|UniProtKB:Q53TN4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66525;
CC Evidence={ECO:0000250|UniProtKB:Q53TN4};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000250|UniProtKB:Q53TN4};
CC Note=Binds 2 heme b groups non-covalently.
CC {ECO:0000250|UniProtKB:Q53TN4};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q53TN4}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q53TN4};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q53TN4}. Apical cell
CC membrane {ECO:0000250|UniProtKB:Q53TN4}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q53TN4}. Note=Localized at the brush border of
CC duodenal cells. {ECO:0000250|UniProtKB:Q53TN4}.
CC -!- TISSUE SPECIFICITY: Highly expressed in all regions of the small
CC intestine and colon studied in suckling animals. However, after
CC weaning, when iron absorption declines significantly, strong expression
CC is retained only in the duodenum. Also expressed in respiratory
CC epithelium. {ECO:0000269|PubMed:16510471, ECO:0000269|PubMed:17627967}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC085768; AAH85768.1; -; mRNA.
DR RefSeq; NP_001011954.1; NM_001011954.1.
DR AlphaFoldDB; Q5RKJ2; -.
DR SMR; Q5RKJ2; -.
DR STRING; 10116.ENSRNOP00000012942; -.
DR PhosphoSitePlus; Q5RKJ2; -.
DR PaxDb; Q5RKJ2; -.
DR Ensembl; ENSRNOT00000012942; ENSRNOP00000012942; ENSRNOG00000009620.
DR GeneID; 295669; -.
DR KEGG; rno:295669; -.
DR UCSC; RGD:1305740; rat.
DR CTD; 79901; -.
DR RGD; 1305740; Cybrd1.
DR eggNOG; KOG1619; Eukaryota.
DR GeneTree; ENSGT00950000183197; -.
DR HOGENOM; CLU_069712_1_2_1; -.
DR InParanoid; Q5RKJ2; -.
DR OMA; SAEFNWH; -.
DR OrthoDB; 1503869at2759; -.
DR PhylomeDB; Q5RKJ2; -.
DR TreeFam; TF314222; -.
DR Reactome; R-RNO-917937; Iron uptake and transport.
DR PRO; PR:Q5RKJ2; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000009620; Expressed in duodenum and 18 other tissues.
DR Genevisible; Q5RKJ2; RN.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0031526; C:brush border membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0016722; F:oxidoreductase activity, acting on metal ions; ISO:RGD.
DR GO; GO:0140571; F:transmembrane ascorbate ferrireductase activity; ISS:UniProtKB.
DR GO; GO:0140575; F:transmembrane monodehydroascorbate reductase activity; ISS:UniProtKB.
DR GO; GO:0140576; P:ascorbate homeostasis; ISS:UniProtKB.
DR GO; GO:0006879; P:cellular iron ion homeostasis; ISO:RGD.
DR GO; GO:0055072; P:iron ion homeostasis; ISS:UniProtKB.
DR GO; GO:0010039; P:response to iron ion; ISO:RGD.
DR InterPro; IPR043205; CYB561/CYBRD1-like.
DR InterPro; IPR028838; CYBRD1.
DR InterPro; IPR006593; Cyt_b561/ferric_Rdtase_TM.
DR PANTHER; PTHR10106; PTHR10106; 1.
DR PANTHER; PTHR10106:SF12; PTHR10106:SF12; 1.
DR Pfam; PF03188; Cytochrom_B561; 1.
DR SMART; SM00665; B561; 1.
DR PROSITE; PS50939; CYTOCHROME_B561; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Electron transport; Heme; Iron; Membrane; Metal-binding;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Translocase;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..286
FT /note="Plasma membrane ascorbate-dependent reductase
FT CYBRD1"
FT /id="PRO_0000314833"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 8..32
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TOPO_DOM 33..47
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 48..69
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TOPO_DOM 70..78
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 79..105
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TOPO_DOM 106..118
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 119..144
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TOPO_DOM 145..151
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 152..179
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TOPO_DOM 180..197
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TRANSMEM 198..222
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT TOPO_DOM 223..286
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT DOMAIN 15..220
FT /note="Cytochrome b561"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00242"
FT BINDING 50
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="1"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 70
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 79
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 79
FT /ligand="L-ascorbate"
FT /ligand_id="ChEBI:CHEBI:38290"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 83
FT /ligand="L-ascorbate"
FT /ligand_id="ChEBI:CHEBI:38290"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 86
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="2"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 108
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_note="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 115..118
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 120
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="1"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 152
FT /ligand="L-ascorbate"
FT /ligand_id="ChEBI:CHEBI:38290"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 159
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="2"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 180
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT BINDING 225
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT MOD_RES 232
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT MOD_RES 285
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q53TN4"
SQ SEQUENCE 286 AA; 31519 MW; 38B043EDDA187916 CRC64;
MAMEGYRGFL GLLVSALLVG FLSVIFVLIW VLHFREGLGW DGGALEFNWH PVLAVTGFVF
IQGIAIIVYR LPWTWKCSKF LMKSIHAGLN AVAAILAIIS VVAVFDYHNV RKIPHMYSLH
SWVGLTVLIL YIQQLVVGFF IFLLPWAPPS LRAIVMPIHV YSGLLLFGTV IATVLMGVTE
KLFFVLKNPS YHSFPPEGVF TNTLGLLILV FGALIFWIVT RPQWKRPREP GSIPLQLNGG
NADGMEGAIA ISSAHNMDAA DAELSSEGAA RKRTLGLVDT GQRSTM
